Integrated Free-standing Nanoprobes for Neuroscience and Beyond Abstract A central theme of this proposal is to explore the unique capabilities of nanotechnology to create powerful neuroprobes that can break the boundaries of traditional technologies. Previous efforts in nanodevices focus on "on-chip" integration, which requires bulk substrate support and bulk external electrodes like any conventional devices, resulting in functional systems much larger than the active devices, and therefore losing the intrinsic merit of "NANO". Here I propose an entirely new generation of nanoscale probes ("nanoprobe") that are fully integrated (with all necessary functions built in the nanostructure itself and requires no external electrodes for power input or signal output), free standing (requires no supporting substrate), highly sensitive and minimally invasive. The proposed nanoprobe integrates nanoscacle potential sensor (nanoFET: field-effect transistor), power source (photodiode), and signal output (nanoLED: light emitting diode) in a single nanowire to form a standalone functional nanosystem. The nanoprobe is powered by photodiodes; and current flow through the circuit is controlled by nanoFET potential sensor whose resistance can vary in responding to nearby potential change (e.g. neuronal action potential or binding of charged molecules/ions); and signal output is monitored by nanoLED emission intensity, which is proportional to current flow through the circuit. The proposed nanoprobe is the first free-standing active nanodevice of its kind with fully integrated functionalities. The successful development of such nanoprobes represents the beginning of a new paradigm for nanoscale devices as minimally invasive biological probes. The integration of multiple functions in a single nanostructure enables TRUE nanoscale probes for detecting, monitoring and manipulating electrophysiological signals with unprecedented sensitivity, spatiotemporal resolution and throughput. The development of integrated nanoprobe and its derivatives can create a new platform technology for fundamental studies to unravel biological problems and biomedical applications including disease detection, prevention and therapy, and therefore impact broadly from neuroscience to biomedicine in general.